Contact lenses require an effective disinfection regimen to kill any harmful microorganisms that may be present or grow on the lenses, and thus pose a danger of serious eye infections and other health problems for the user. This is particularly true with respect to contact lenses made from hydrophilic materials. Harmful organisms which may be present on contact lenses or other eye care products such as lens cases include Serratia marcescens, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans. Likewise, other products, such as eye care solutions, which are susceptible to contamination by harmful organisms must be disinfected prior to use.
A number of methods for disinfecting contact lenses have been proposed, including the use of high temperatures, oxidative chemicals, and antimicrobial agents. U.S. Pat. Nos. 4,407,791 and 4,525,346 show the polyquaternary ammonium contact lens disinfecting agent 1-tris(2-hydroxyethyl)ammonium-2-butenyl-4-poly[1-dimethyl ammonium-2-butenyl]-.omega.-tris(2-hydroxyethyl)ammonium chloride salt. European patent application 89810477.3 shows the disinfecting agent dodecyl-dimethyl-(2-phenoxyethyl)-ammonium bromide. U.S. Pat. No. 4,029,817 assigned to Allergan, Inc. shows the contact lens disinfecting agent tallow triethanol ammonium chloride. U.S. Pat. No. 4,758,595 shows the hexamethylene biguanide contact lens disinfecting agent.
Other types of agent have been examined for anti-microbial activity in vitro. For example, various surface-active peptides have been studied. Some of these peptides require a specific conformation. Others, such as cationic wide-range cytolytic peptides, are less reliant on specific conformations. These peptides appear to target the cellular lipid bilayer membrane, and to modulate membranal potential, permeability and function. One possible mechanism is thought to be formation of ion channels in the membrane, which causes lysis and cell death. Examples of the foregoing peptides include naturally occurring compounds such as cecropins, defensins, magainins, sarcotoxins, and melittins.
Certain cytolytic peptides have also been shown to possess anti-microbial activity in vitro as both the natural, all-L peptides and as the synthetic, all-D enantiomers. For example, in Wade et al., Proc. Natl. Acad. Sci. USA 87, 4761-4765 (JUNE 1990), inhibition zone assays using thin agarose plates were carried out for all-D cecropin A, magainin 2 amide, melittin and certain cecropin-melittin hybrids. Standard anti-microbial activity assays were also carried out by Bessale et al., FEBS Letters 274, no. 1,2, 151-155 (November 1990) (hereinafter "Bessale I") for all-D magainin-2. The all-D enantiomers were also found to resist enzymatic cleavage, for example by trypsin, in vitro. No mention is made, however, of the use of these enantiomeric anti-microbial peptides in formulations such as disinfection formulations, nor of the use of such peptides in combination with proteolytic enzymes.
Contact lenses also require cleaning to remove soilants. For example, in the normal course of wearing contact lenses, tear film and debris consisting of proteinaceous, oily, sebaceous, and related organic matter have a tendency to deposit and build up on lens surfaces. As part of the routine care regimen, contact lenses must be cleaned to remove these tear film deposits and debris. If these deposits are not properly removed, both the wettability and optical clarity of the lenses is substantially reduced causing discomfort for the wearer.
The only safe and effective means found to date for removing protein build-up is the use of enzymes, whose hydrolytic activity reduces the proteinaceous materials to small, water soluble subunits. Particularly useful are proteolytic enzymes or proteases. U.S. Pat. No. 3,910,296 discloses the use of proteases for cleaning contact lenses.
New methods have been developed which can remove proteinaceous material from contact lenses while disinfecting the lenses. For example, U.S. Pat. No. 4,614,549 discloses a single-step method of cleaning and disinfecting contact lenses in aqueous solutions of proteolytic enzymes at temperatures of between 60.degree. C. and 100.degree. C. This method requires the use of electrical disinfecting apparatus and elevated temperatures. U.S. Pat. No. Re. 32,672, assigned to Allergan, Inc. discloses a method by which the lenses are immersed in a solution containing peroxide and a peroxide-active enzyme. Japanese patent application Showa 49-45012 discusses cleaning and sterilizing contact lenses by contacting the lens with an aqueous solution containing a protease and sterilizing agent such as triethanol tallow ammonium chloride, thimerosal and a wide range of reducing agents.
U.S. Pat. No. 5,096,607, to Mowrey-McKee et al., discloses a method for simultaneously cleaning and disinfecting contact lenses by contacting the lenses with a solution containing a proteolytic enzyme and a disinfecting agent which is either a polymeric quaternary ammonium salt or a biguanide, and adjusting the osmotic value of the solution to a level which does not inhibit the activity of the quaternary ammonium salt or the biguanide. This patent describes a wide range of useful proteolytic enzymes (in kind and amount) and a wide range of quaternary ammonium salts and biguanides (in kind and amount). None of the disinfecting agents are peptides, however, as such would be expected to be subject to attack by the proteolytic enzyme.